The fight against malaria in Tanzania was facing drawbacks due to the presence of mosquitoes that can build resistance against insecticides used in bed nets.
However, that’s about to change following new findings by scientists showing that a newly found class of bed nets can neutralise the ability of mosquitoes to resist the insecticides known as pyrethroid.
This, according to the study the scientists published in the Lancet Journal on Wednesday, can significantly reduce malaria infection in children.
The scientists carried out a two-year community randomised trial involving more than 15,000 children in Tanzania.
During the trial, a long lasting insecticidal net was treated with a substance known as piperonyl butoxide (PBO LLIN) which reduced the prevalence of malaria by 44 per cent and 33 per cent in the first and second year respectively.
This was in comparison with to a standard long lasting insecticidal net (LLIN) treated with pyrethroid only.
The study, led by the London School of Hygiene and Tropical Medicine (LSHTM), also showed unprecedented malaria control through indoor residual spraying (IRS).
This was though an insecticide known as pirimiphos methyl, which after a single spray round reduced malaria infection by 48 per cent for an entire year.
Both LLINs and IRS are the cornerstones of malaria control in sub-Sahara Africa, and have been estimated to reduce malaria disease by 41 per cent and malaria deaths by 62 per cent between 2000 and 2015 globally.
Malaria still kills nearly half a million people annually, and for the first time in many years the World Health Organization (WHO) reported an increase in malaria cases and no change in the number of malaria deaths in 2017.
There is concurrent evidence that resistance to pyrethroid insecticide is growing in the Anopheline mosquitoes which transmit the disease, various scientific reports show. Scientists say there is only a limited range of alternative insecticides available, particularly for LLINs for which the insecticides known as pyrethroids are the only class of insecticide fully recommended by the WHO.
For almost 20 years, the WHO and the London School of Hygiene and Tropical Medicine have been collaborating with the chemical industry to develop new types of LLIN and new insecticides for indoor residual spray.
They had anticipated the possible failure of current control tools due to resistance.
One of these is a long lasting insecticide net which incorporates the substance known as piperonyl butoxide (PBO), a chemical which blocks the natural defense mechanisms of insects. This now means the pyrethroid on the LLIN remains potent against mosquitoes despite resistance.
This chemical synergist, scientists say, stops insects from breaking down the pyrethroid within their bodies, so the insecticide stays toxic to the insect.
Carried out in Muleba, Tanzania
Dr Natacha Protopopoff from the London School of Hygiene and Tropical Medicine who led the field research operations in Muleba, Tanzania, said: “It’s imperative we try and remain one step ahead of insecticide resistant mosquito which threatens to reverse the great gains made in combating malaria.” She adds: We must develop an improved strategy based on new classes of LLIN to control malaria transmitted by pyrethroid resistant mosquitoes.
This new study involved randomly selected children aged six months to 14 years from villages in Muleba district of North West Tanzania, where high levels of resistance to pyrethroids have been reported.
How it was done
In 2015, 48 villages were randomly categorized into four groups with different preventative measures. Altogether 45,000 standard LLINs and 45,000 PBO LLINs were distributed. Children were then tested for malaria at the end of each rainy season.
After nine months, malaria infection was considerably lower in the group that received just the net treated with piperonyl butoxide – PBO LLIN - (31.1 per cent) and the group that received indoor residual spraying and standard LLIN (28.7 per cent) compared to the group that received standard LLIN alone (55.3 per cent).
Twelve months later, the PBO LLIN effect was still persisting relative to the standard LLIN.
To strengthen the evidence for the interventions, mosquito traps were placed in each study arm. The number of malaria infected mosquitoes captured in the PBO LLIN villages was reduced by 87 per cent and 67 per cent during the first and second years respectively compared to the standard LLIN villages.
Professor Mark Rowland from LSHTM and Principal Investigator, said: “This project is a game-changer.”
He added, “The trial is the first clear evidence that nets treated with piperonyl butoxide can significantly improve personal and community protection from malaria compared to standard pyrethroid-only nets in areas where there is high pyrethroid resistance.”
He said, “It also demonstrated that pyrethroid resistance is now a significant problem in some areas and standard LLIN are less effective than before, and that the new IRS controlled malaria for an entire year before needing to be re-sprayed.”
As a direct consequence of the trial, WHO revised its recommendations on LLIN in September 2017, giving an interim policy recommendation to PBO LLIN as a new class of bed nets known as LLIN1.
According to the Coordinator for Entomology and Vector Control in the WHO Global Malaria Programme, Dr Jan Kolaczinski, the WHO recommends that PBO LLINs should be deployed for malaria prevention in areas where mosquitoes are pyrethroid resistant.
However, he stresses that full coverage should be maintained. This would include many endemic areas in Africa where standard LLINs are currently used.
Professor Rowland adds: We are pleased that the WHO has already revised policy on the basis of this trial. This will ensure insecticide treated nets will remain an effective intervention for malaria control, and justifies the continued investment and research on alternative insecticides for use on nets.”
Is the study all-perfect? No
The authors acknowledge that the study does have limitations, including the short buffer distance between villages; however, any spill-over between villages would tend to undermine the intervention effect rather than increase it.
The authors also stress that it is important to always sleep under a bed net in areas of malaria transmission. They say that until PBO LLIN are deployed more widely in areas of resistance, standard pyrethroid-only nets will be more protective than non-use of nets and should continue to be used.
The study was funded by the Joint Global Health Trials Scheme of the Department for International Development, the Medical Research Council and Wellcome Trust.